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Nov 5

SRT1720 is a sirt1 activator and the new hope for a calorie restriction mimicker, which may lead to an increase in human lifespan.

Resveratrol (which I have written about several times, here, here and here) is also a sirt1 activator, which is found (in very small quantity) in red wine,  is also a sirt1 activator and has been tested multiple times to see what it can do for animal’s health and survival (see below). The interesting thing about SRT1720 is that it works at a 1,000 times lower dose than resveratrol.

A new paper examining SRT1720 was published in cell metabolism and covered at eurakalert and wired.

In mice fed a high fat diet (very similar to the resveratrol study) SRT1720 spared the animals from gaining as much weight (even though they ate the same amount) and becoming insulin resistant. Additionally, the animals fed SRT1720 had greater running endurance (no great surprise since they were not overweight). Overall, the authors providing supporting data for the mechanism behind these affects is due to increased fatty acid oxidation (which should help endurance beyond just being a lighter weight) (the same thing exercise does).

Hmmm this sounds just like the recent paper I did on human exercise. Exercise in humans leads them to become less energy efficient at rest - as there was a decoupling of food intake and energy output (occurs in the mitochondria) and hence the extra energy is burnt off as heat. That is why you can eat more if you are on an exercise program and not gain weight (compared to your twin that is not exercising). This goes beyond just the extra calories you are burning while actually exercising. Your entire muscle metabolism becomes less efficient and you need more food to get the same amount of ATP. And while this sounds bad - there are obvious benefits once your muscles have to start working.

Back to RST1720 you must remember the results reported are for mice on a high fat diet. Resveratrol when tested on mice on a high fat diet improved health and survival (meaning the mice on this diet lived longer). When resveratrol was tested for its effect on lifespan on mice fed a ‘normal’ diet there was no effect (but the diet was not started until 12 months of age - it would be interesting to see if it would work when started earlier).

Take home message:

SRT1720 holds promise as it did prevent excessive weight gain and improved endurance, and appears to be an advance over resveratrol as it is 1,000 times more potent (hence I am guessing would be more economically viable). And combined with previous resveratrol studies is likely to increase the lifespan of animals on a high fat diet. The big question is will SRT1720 extend the lifespan of animals on a ‘normal diet’? This is the holy grail of calorie restriction mimickers. Time will tell.

Oct 30

I am always encouraging people to exercise for the general and brain health. Research has demonstrated that exercise obviously improves muscle function and your performance. Additionally, while exercising a trained individual is more efficient biomechanically and biochemically (including increased fat oxidation and number of mitochondria).

However, an unanswered question is the difference between trained and untrained sedentary individuals while at rest (in vivo).

Befroy et. al., PNAS, 2008 (open access) examined this question and the result have some interesting implications. They had 8 control subjects and 7 athletes of similar age (26), weight and BMI. The athletic group had to be performing 4 or more hours of running, or running based sports, per week. The peak VO2 max in the trained group averaged 60.9 which is considerably higher than normal sedentary peak of 30-40 (though they don’t report the exact numbers for the control group).

They measured mitochondrial oxidative function by examining the flux through the tri-carboxylic acid (TCA) cycle using magnetic resonance spectroscopy (MRS). They also importantly measured the rate of muscle ATP synthesis using MRS.

Results:

At rest (important distinction compared to more active) substrate oxidation via the TCA cycle was 54% higher in the muscles of the trained group. So with a 54% increase in substrate (fat and carbohydrates) oxidation what do you think would happen with muscle energy (ATP)?

Interesting part:

Muscle ATP synthesis at rest were not different between the trained and untrained group – despite the 54% increase in mitochondrial oxidation rate in the TCA cycle. Hence, it appears as if the trained group have a reduced muscle energy efficiency compared to the untrained.

The authors conclude that:

… there is an uncoupling of oxidation from energy production in endurance-trained muscle at rest.

Of course in the discussion they are trying to explain the lack of enhanced ATP in the trained group at rest – but in reality the body doesn’t need the extra energy. Sure the trained body has a greater number of engines (mitochondria) – but at rest there is relatively little need for all these energy producers. The authors suggest that, somewhat paradoxically, at rest the trained mitochondria become less efficient and go into a greater uncoupling state.

The results are consistent with the general literature of increased mitochondrial numbers, which would allow a higher rate of flux of the TCA cycle. These overall changes would allow a higher capacity for fatty acid oxidation and ATP production under high demand (e.g. running). Since the trained group has more mitochondria but at rest the muscle requires the same amount of energy (ATP) as the untrained group each mitochondria in the trained group is producing less energy per unit compared to the untrained. Hence, in the trained energy production at rest is less efficient. The decrease in energy efficiency results in an increase in basal TCA cycle flux and oxygen consumption.

Wow ! – that doesn’t sound good. Exercise and become less efficient – use more substrate (carbohydrates and fats) and a greater amount of oxygen but get the same amount of energy.

However, the elevation of TCA flux may also be a benefit when starting an exercise bout as one could more quickly ramp up ATP production. And from previous research we know that once you get beyond the resting state the trained system kicks in and will easily outperform the untrained one.

Other considerations:

But these results might also explain how we hear so many stories of overweight people not eating much but still gaining weight (or at least not losing weight) compared to lighter, more in shape individuals who can eat a ton and not gain weight. The overweight out of shape individual would have a more efficient mitochondria – extracting a higher percentage of energy per food unit compared to the trained individual.

Additionally, the uncoupling in the trained individual would result in high heat production from the uncoupling process. Looking at this evolutionary heat production was very important as we migrated to cooler climates. So the ‘wasted’ energy of inefficient trained muscles wouldn’t really be such a waste since it would be a possible benefit. In our modern world of climate controlled houses this is not a concern.

Many of you might have observed that on a cool fall day it is the ‘less trained’ individuals wearing warmer clothes including hats, gloves etc – while you can spy these slim runner types walking around in a t-shirt. The above at rest muscle energy inefficiency and subsequent increased excess heat production could be an explanation.

I would even offer the hypothesis that the individual can tell their level of fitness by the changes they notice in level of clothing they require during the cool/cold season.

Take home message:

Exercise can make your at rest energy production less efficient (compared to untrained) – due to the fact the muscles don’t require much energy in this state. And while being less efficient sounds bad – once you ramp up energy need (as required to do physical work – and for survival in our past) the trained system outperforms the untrained. As an added bonus – that was probably vital to survival in the past – the inefficient energy system produced by training (or trying to live in the past) results in extra heat production  at rest.

Additionally, the results from the paper might help explain why it is easy to keep lean if you exercise (more wasted energy in the form of heat) and hard to reduce weight if you are in an untrained state. So to lose weight start exercising so you become less energy efficient – I know that sounds weird.

How much clothing are you wearing walking around outside this fall?

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Oct 20

Today’s piece is not high level neurobiology, more like some thoughts on simple everyday approach to life.

I have written previously about the importance of consistency in regards to exercise (and see the piece by Alan Couzens), which I think is related to moderation.

I have two examples where I recently didn’t practice moderation, one story you are likely familiar with, another might be new to you.

Lack of Moderation # 1:

My first moderation story resolved around drinking wine. I hadn’t drank any alcohol for the last 5 months (other than a glass of wine with dinner for 3 nights), but that changed recently when I was invited over to dinner with friends I hadn’t seen in a long time. Long story short is I drank too much wine and stayed up too late. The next day I suffered the consequences, and the day was a write off for getting something productive done.

Lack of Moderation # 2:

The second incidence occurred this weekend and had nothing to do with alcohol intake. I went on a long run/hike of 4+ hours. I am currently in reasonable shape due to a consistent running program of a 5-6 day week of 30 minutes to 1 hour of running, but not too much long stuff. Normally, a 4+ hour endeavor like this would not have been a problem, but the intensity was also very high. Longer than normal length and higher than normal intensity is a bad combination.

When I made it back home the next 4 hours were lost as I was sprawled out on the couch drinking plenty of fluids (sounds very similar as a night of too much alcohol intake). I was not capable of (or at least didn’t have the motivation) mental work that I should have been doing. I am not sure this is true for everybody but if I am wiped out physically I am not able to do serious mental work (maybe tied in with my whole D2 information brain efficiency theory.  So, much like a hangover there was loss of production. By the time I semi-recovered at night all I managed was some light reading.

Moderation when starting an exercise program:

Normally, I tell friends if they are starting a new exercise program after a layoff is to start with far less, and far easier, than what they think they should do. Many times you go through your first exercise session and it feels like you didn’t do anything, but 24 or 48 hours later the pain sets in. The problem with this is if you are sore you might have less incentive to get the next workout in.

Now in my situation while I had been on a regular running program the length and intensity was more than my body is currently use to. I knew I was in trouble when the pain started while running downhill (eccentric exercise produces a high level of muscle damage) even during the outing, compared to 1 or 2 days later. So you really know you have overdone it if the pain has set in during your exercise bout. I knew early on that the day was probably going to be too much, but I really wanted to test myself on this run/hike because it was one I did on a fairly regular basis 13 or so years ago. This is a hike I would take my friends on when we were in our twenties. The only good news despite going fairly fast I never felt like I needed to take a stop to catch my breath, while I remember every one of my friends when they were in their twenties having to stop several times just to have a chance at making it to the top.

Recovery in your 20’s compared to out of your 20s:

In your twenties moderation is less of an issue, you recover better from a night of high alcohol intake (maybe because they are in serious ‘training’ by consistent intake), and from excessive bouts of exercise. I know in my twenties even if I wasn’t doing regular exercise I could have attacked this hike/run (ok it would have only been a hike) and not suffered.

Once past your twenties (potentially even your late 20s) it would be wise to start practicing moderation – at least if you don’t want to lose too many productive hours. The other argument is in certain cases it might be worth it. For me I guess the beautiful run/hike that included running through a forest with no one in sight, and the stunning view at the top, and a chance to test myself was worth it in this case – but there was a cost.

(update: suprisingly I was able to get in a run 24 hours after my over exercetion but currently 40 hour after my legs are quite tender so at best it will be another slow jog tonight - 2 days latter and I am still paying the cost of not practicing moderation).

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Sep 9

You might be scratching your head over my title but hopefully it will make sense at the end.

We all now the importance of exercise for both our body and mental health. You can’t go a week or so without hearing about the latest research that provides evidence for what we all know at a common sense level. Keep on moving (run, bike, swim, jump, play sports, anything) so you don’t slow down as you age (or at least a slower rate of slowing) and this same moving is good for your brain on many levels (more neurogenesis, less depression, better memory, less Alzheimer, etc, etc).

Money savings vs fitness savings

The nice thing about making monthly deposit into your long term saving plan is you see it steadily buildup and it doesn’t go away unless you decide to spend it (or some other economic catastrophe). However, the deposit you make into your bodies exercise bank is quite different. Yes, over time regular exercise will build up your fitness bank - you get fitter and fitter. The problem is when you stop doing those daily/weekly deposit your fitness bottom line stops dropping. While if you happen not to make a deposit into your long term saving account your bank balance does not start decreasing (unless those pesty bank keep on charging you fees, but even this would be balanced out by your interest payments). With your money - the old rule is with normal interests rates you should double your money every 7-14 years. Not true with fitness unless you keep up your routine you start sliding backwards.

For an excellent post on the importance of consistence exercise and the physiology behind lost fitness if you take a break check out Alan Couzens piece here.

So for money if you stop making deposits your account doesn’t start going backwards, but your fitness/health account starts reversing after a week or so of no exercise. Hence, the importance of consistency in your fitness routine.

A money saving method to help the consistency of your fitness account.

Some new research looking at money saving, by people who have trouble with this part of their life, found that those that plan their saving more than a month in the future did worse than those that plan only a month at a time (via esciencenews.com).

While keeping the savings goal in mind, planning to save in a shorter time frame, like one month, leads to the most success, said Tam. “This type of time frame helps people see steady progress along the way while not feeling too much pressure. This is similar to some of the dieting regimens – not too close so you don’t see progress but not too far away either so you don’t get discouraged.”

I found the importance of time-frame very interesting. Tam, one of the authors of the presentation/paper points out above the similar finding in dieting. So I wonder if the same principle would also hold for fitness routines?

As I have blogged about previously there seems to evidence suggesting getting in 45 minutes of exercise per day 6 days a week which equates to 4.5 hours per week. Now the question is should we think about daily (45 minutes), weekly (4.5 hours), monthly (18 hours), or yearly (216 hours)? Is money different because normally we are getting paid every 2 weeks and we make these saving choices - at least deposit into your bank account once or twice a month. So you could argue that money saving is quite different than the daily choice to exercise or not. But in reality to make those saving goals you have to make appropriate money spending choices each day (go out for dinner, buy the latest gadget, etc).

Something to try:

So if you are struggling to meet your fitness saving - constant banking - then you might try out this approach. Pick a monthly goal of how much exercise you would like to do - then keep track and chart your health saving each month.

To higher money and fitness savings (though for fitness you have to keep it up).

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